SEARCHNARRATIVE_REVIEWoncology, immunology

narrative_review·oncology, immunology, preclinical research, biomedical research·PMC10384176

Hacking the Immune Response to Solid Tumors: Harnessing the Anti-Cancer Capacities of Oncolytic Bacteria

Pharmaceutics · 9 authors, 5 centres

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TL;DR

This review examines how bacteria that naturally target tumors can be engineered to stimulate anti-cancer immune responses. It summarizes known mechanisms and the clinical use of the BCG vaccine for bladder cancer.

Full summary

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This narrative review discusses oncolytic bacteria, a class of microorganisms with a natural ability to target solid tumors and stimulate immune responses. The authors detail the mechanisms of bacteria-host immune interactions, focusing on membrane molecules that trigger oncolytic effects and localized/systemic immunogenic responses. A key example highlighted is the Bacille Calmette-Guerin (BCG) vaccine, which has been a successful immunomodulatory treatment for non-muscle-invasive bladder cancer for decades. The review also covers advancements in genetic engineering aimed at enhancing the anti-cancer capacities of these bacteria for clinical translation, including strains that have reached Phase III trials. It concludes that a complete understanding of these interactions is necessary to unlock their full therapeutic potential.

STUDY TYPE

narrative_review

SPECIALTY

oncology

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10384176

Hacking the Immune Response to Solid Tumors: Harnessing the Anti-Cancer Capacities of Oncolytic Bacteria

Pharmaceutics

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ABSTRACT

Oncolytic bacteria are a classification of bacteria with a natural ability to specifically target solid tumors and, in the process, stimulate a potent immune response. Currently, these include species of Klebsiella , Listeria , Mycobacteria , Streptococcus / Serratia (Coley’s Toxin), Proteus , Salmonella , and Clostridium . Advancements in techniques and methodology, including genetic engineering, create opportunities to “hijack” typical host–pathogen interactions and subsequently harness oncolytic capacities. Engineering, sometimes termed “domestication”, of oncolytic bacterial species is especially beneficial when solid tumors are inaccessible or metastasize early in development. This review examines reported oncolytic bacteria–host immune interactions and details the known mechanisms of these interactions to the protein level. A synopsis of the presented membrane surface molecules that elicit particularly promising oncolytic capacities is paired with the stimulated localized and systemic immunogenic effects. In addition, oncolytic bacterial progression toward clinical translation through engineering efforts are discussed, with thorough attention given to strains that have accomplished Phase III clinical trial initiation. In addition to therapeutic mitigation after the tumor has formed, some bacterial species, referred to as “prophylactic”, may even be able to prevent or “derail” tumor formation through anti-inflammatory capabilities. These promising species and their particularly favorable characteristics are summarized as well. A complete understanding of the bacteria–host interaction will likely be necessary to assess anti-cancer capacities and unlock the full cancer therapeutic potential of oncolytic bacteria.

CITATION EXPORT

Jason M. Roe, Kevin Seely, Caleb J. Bussard et al.. Hacking the Immune Response to Solid Tumors: Harnessing the Anti-Cancer Capacities of Oncolytic Bacteria. Pharmaceutics. (2023). https://doi.org/10.3390/pharmaceutics15072004

AUTHORS

9 · 5 CENTRES

Jason M. Roe, Kevin Seely, Caleb J. Bussard, Emily Eischen Martin, Elizabeth G. Mouw, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks, Kaitlin M. Dailey

1College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA
2College of Osteopathic Medicine, Rocky Vista University, Parker, CO 80130, USA
3Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
4Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE 68198, USA
5Office of Research & Scholarly Activity, Rocky Vista University, Ivins, UT 84738, USA

EDITOR / REVIEWER

Joseph Anthoney Vetro